Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Glycogen storage disease type IV due to branching enzyme deficiency was found in an inbred family of Norwegian forest cats, an uncommon breed of domestic cats. Skeletal muscle, heart, and CNS degeneration were clinically apparent and histologically evident in affected cats older than 5 mo of age, but cirrhosis and hepatic failure, hallmarks of the human disorder, were absent. Beginning at or before birth, affected cats accumulated an abnormal glycogen in many tissues that was determined by histochemical, enzymatic, and spectral analysis to be a poorly branched alpha-1,4-D-glucan. Branching enzyme activity was less than 0.1 of normal in liver and muscle of affected cats and partially deficient (0.17-0.75 of normal) in muscle and leukocytes of the parents of affected cats. These data and pedigree analysis indicate that branching enzyme deficiency is a simple autosomal recessive trait in this family. This is the first reported animal model of human glycogen storage disease type IV. A breeding colony derived from a relative of the affected cats has been established.
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PMID:Glycogen storage disease type IV: inherited deficiency of branching enzyme activity in cats. 133 88

Morphological observations of paraffin-embedded histological sections stained with H&E led to the discovery of some cytoplasmic changes which occur in different conditions, although they look alike under the light microscope. These hepatocytic changes consisted basically of homogeneous areas which are weakly eosinophilic in H&E-stained sections. They are frequently referred to as "inclusion" bodies, even when they are not true inclusions. The hepatocytic changes observed in HBsAg carriers, in chronic alcoholic patients treated with cyanamide to discourage them from drinking alcohol, in Lafora's disease, and in glycogenosis type IV, look very similar in paraffin sections stained with H&E. Nevertheless, they can be differentiated using ancillary techniques. On electron microscopy they do not look alike. Of particular interest are the "inclusion" bodies induced by cyanamide, a predictable and reproductible lesion, which in man eventually leads to cirrhosis. Other types of hepatocytic changes also giving a rather vague "ground-glass" appearance to the cytoplasm are those resulting from intracytoplasmic accumulation of proteins, particularly fibrinogen, and those observed in patients treated with different drugs.
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PMID:Ground-glass hepatocytes: light and electron microscopy. Characterization of the different types. 196 81

Glycogen storage disease type IV is rare. The disease is characterized by widespread storage of a polysaccharide similar to amylopectin. An autopsy case of a 6-year-old Thai boy with cirrhosis and deposits in the liver, heart, muscle and central nervous system was described along with histochemical and electron microscopic findings.
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PMID:Type IV glycogen storage disease: first reported case in Thailand. 262 38

A neonate with deficiency of branching enzyme (glycogenosis type IV) presented symptoms of severe hypotonia pre- and postnatally, and dilated cardiomyopathy in early infancy. The classical clinical manifestation of liver cirrhosis was not present, although amylopectin-like inclusions were found in the hepatocytes. In contrast to a previous report, the neurons in the brain stem and spinal anterior horns contained PAS-positive, diastase-resistant deposits. The combined involvement of the muscles and motor neurones could account for the severity of hypotonia. The muscle biopsy, electromyogram and biochemical and enzyme assays were helpful in establishing the diagnosis.
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PMID:Neonatal hypotonia and cardiomyopathy secondary to type IV glycogenosis. 805 7

The development of hepatocellular adenoma has been recognized in association with glycogen storage disease type I and, less often, with glycogen storage disease type III, but, to our knowledge, it has not been reported in glycogen storage disease type IV. We had the opportunity to study an 11-month-old male infant who underwent orthotopic liver transplantation for cirrhosis that developed in the setting of glycogen storage disease type IV. A clinically unsuspected hepatocellular adenoma was present in the explanted liver. Glycogen storage disease type IV should be considered as a potential precursor to the development of hepatocellular adenoma. Recognition of this association is important, both in terms of the differential diagnosis of tumors that occur in this setting and also to anticipate potential complications of this benign neoplasm.
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PMID:Hepatocellular adenoma in glycogen storage disease type IV. 828 39

Glycogen storage disease type IV (GSD-IV) is an autosomal recessive disease resulting from deficient glycogen-branching enzyme (GBE) activity. The classic and most common form is progressive liver cirrhosis and failure leading to either liver transplantation or death by 5 yr of age. However, the liver disease is not always progressive. In addition, a neuromuscular type of the disease has been reported. The molecular basis of GSD-IV is not known, nor is there a known reason for the clinical variability. We studied the GBE gene in patients with various presentations of GSD-IV. Three point mutations in the GBE gene were found in two patients with the classical presentation: R515C, F257L, and R524X. Transient expression experiments showed that these mutations inactivated GBE activity. Two point mutations, L224P and Y329S, were detected in two separate alleles of a patient with the nonprogressive hepatic form. The L224P resulted in complete loss of GBE activity, whereas the Y329S resulted in loss of approximately 50% of GBE activity. The Y329S allele was also detected in another patient with the nonprogressive form of GSD-IV but not in 35 unrelated controls or in patients with the more severe forms of GSD-IV. A 210-bp deletion from nucleotide 873 to 1082 of the GBE cDNA was detected in a patient with the fatal neonatal neuromuscular presentation. This deletion, representing the loss of one full exon, was caused by a 3' acceptor splicing site mutation (ag to aa). The deletion abolished GBE activity. Our studies indicate that the three different forms of GSD-IV were caused by mutations in the same GBE gene. The data also suggest that the significant retention of GBE activity in the Y329S allele may be a reason for the mild disease. Further study of genotype/phenotype correlations may yield useful information in predicting the clinical outcomes.
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PMID:Hepatic and neuromuscular forms of glycogen storage disease type IV caused by mutations in the same glycogen-branching enzyme gene. 861 47

The classic clinical presentation for type IV glycogen storage disease (branching enzyme deficiency, GSD IV) is hepatosplenomegaly with failure to thrive occurring in the first 18 months of life, followed by progressive liver failure and death by age 5 years. Although there have been two patients without apparent liver progression previously reported, no long-term follow-up clinical data have been available. We present here the clinical spectrum of the non-progressive liver form of GSD IV in four patients, and long-term follow-up of the oldest identified patients (ages 13 and 20 years). None has developed progressive liver cirrhosis, skeletal muscle, cardiac or neurological involvement, and none has been transplanted. Branching enzyme activity was also measured in cultured skin fibroblasts from patients with the classic liver progressive, the early neonatal fatal, and the non-progressive hepatic presentations of GSD IV. The residual branching enzyme activity in the patients without progression was not distinguishable from the other forms and could not be used to predict the clinical course. Our data indicate that GSD IV does not always necessitate hepatic transplantation and that caution should be used when counselling patients regarding the prognosis of GSD IV. Patients should be carefully monitored for evidence of progression before recommending liver transplantation.
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PMID:Clinical and laboratory findings in four patients with the non-progressive hepatic form of type IV glycogen storage disease. 883 Jan 77

Type IV glycogenosis or Andersen disease is characterized by a deficiency in branching enzyme. This rare disease is exceptionally seen at birth. The clinico-pathological data are then typical: severe hypotonia with hypoventilation and cellular storage, without any hepatosplenomegaly. The stored material is PAS positive, sometimes made of crystals and appeared birefringent under polarized light. Granulo-filamentous inclusions are shown by electron microscopy, essentially observed in muscle and liver without cirrhosis. Death occurs rapidly. The present case was typical. It is the eleventh reported case in the literature.
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PMID:[Congenital variant of type IV glycogenosis. Anatomoclinical report of a case]. 909 Sep 36

Deficiency of glycogen branching enzyme activity causes glycogen storage disease type IV (GSD-IV). Clinically, GSD-IV has variable clinical presentations ranging from a fatal neonatal neuromuscular disease, to a progressive liver cirrhosis form, and to a milder liver disease without progression. Current methods for prenatal and postnatal diagnosis are based on an indirect method of measuring the enzyme activity, which has a limited sensitivity and cannot be used to distinguish patients with these variable clinical phenotypes. In this study, a GSD-IV family with a non-progressive hepatic form of the disease requested prenatal diagnosis. Determination of the branching enzyme activity in cultivated amniocytes showed 20 per cent residual activity overlapping with the level detected in the heterozygotes. Mutation analysis revealed that the fetus carried two mutant alleles, L224P and Y329S, the same as the proband of this family. The fetus was predicted to be affected and postnatally his clinical presentation is consistent with the diagnosis. We conclude that DNA mutation analysis should be used in the prenatal diagnosis of GSD-IV, especially in the situation of high residual enzyme activity.
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PMID:Prenatal diagnosis of glycogen storage disease type IV using PCR-based DNA mutation analysis. 1052 41

Glycogen storage disease type IV or Andersen disease is an autosomal recessive disorder due to deficiency of glycogen branching enzyme. Typically, glycogen storage disease type IV presents with rapidly progressive liver cirrhosis and death in childhood. Variants include a cardiopathic form of childhood, a relatively benign myopathic form of young adults, and a late-onset neurodegenerative disorder (adult polyglucosan body disease). A severe neuromuscular variant resembling Werdnig-Hoffmann disease has also been described in two patients. The objective was to describe two additional infants with the neuromuscular variant and novel mutations in the GBE1 gene. Branching enzyme assay, Western blot, RT-PCR and sequencing were performed in muscle biopsies from both patients. The cDNA of patient 1 was subcloned and sequenced to define the mutations. Muscle biopsies showed accumulation of periodic acid Schiff-positive, diastase-resistant storage material in both patients and increased lysosomal enzyme activity in patient 1. Branching enzyme activity in muscle was negligible in both patients, and Western blot showed decreased branching enzyme protein. Patient 1 had two single base pair deletions, one in exon 10 (1238delT) and the other in exon 12 (1467delC), and each parent was heterozygous for one of the deletions. Patient 2 had a large homozygous deletion that spanned 627 bp and included exons 8-12. Patient 1, who died at 41 days, had neurophysiological and neuropathological features of Spinal Muscular Atrophy. Patient 2, who died at 5(1/2) weeks, had a predominantly myopathic process. The infantile neuromuscular form of glycogen storage disease type IV is considered extremely rare, but our encountering two patients in close succession suggests that the disease may be underdiagnosed.
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PMID:Fatal infantile neuromuscular presentation of glycogen storage disease type IV. 1501 3


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